brii-196/brii-198 for inpatients with covid-19 (an activ-3/tico treatment trial)

Conditions: COVID-19

Summary: this study looks at the safety and effectiveness of brii-196/brii-198 in treating covid-19 in people who have been hospitalized with the infection. participants in the study will be treated with either brii-196/brii-198 plus current standard of care (soc), or with placebo plus current soc. this is activ-3/tico treatment trial h3.

this is a treatment trial of the activ-3/tico master protocol (nct04501978) to evaluate the safety and efficacy of brii-196/brii-198 in hospitalized patients infected with covid-19. this is a randomized, blinded, controlled sub-study of brii-196/brii-198 plus current standard of care (soc) against placebo plus current soc. the placebo arm may be shared across other sub-studies of the activ-3/tico master protocol. when more than one drug is being tested at the same time, participants will be randomly allocated to treatments or placebo. randomization will be stratified by study site pharmacy and disease severity. there are 2 disease severity strata: participants without organ failure (severity stratum 1) and participants with organ failure (severity stratum 2). an independent data and safety monitoring board (dsmb) will regularly review interim analyses and summarize safety and efficacy outcomes. the pace of enrollment with be initially restricted, and there will be an early review of safety data by the dsmb. at the outset of the trial, only participants in disease severity stratum 1 will be enrolled. this will continue until approximately 300 participants are enrolled and followed for 5 days. the exact number will vary according to the speed of enrollment and the timing of dsmb meetings. prior to expanding enrollment to also include patients in disease severity stratum 2, safety will be evaluated and a pre-specified futility assessment by the dsmb will be carried out using 2 ordinal outcomes assessed at day 5. if brii-196/brii-198 passes the futility assessment, enrollment of participants will be expanded, seamlessly and without any data unblinding, to include participants in disease severity stratum 2 as well as those in disease severity stratum 1. future interim analyses will be based on the primary endpoint of sustained recovery and will use pre-specified guidelines to determine early evidence of benefit, harm, or futility for the investigational agent. participants will be followed for 18 months following randomization. this trial will be conducted in several hundred clinical sites. participating sites are affiliated with networks funded by the united states national institutes of health (nih) and the us department of veterans affairs.

Eligibility criteria:
inclusion criteria: * refer to the master protocol (nct04501978) exclusion criteria: * refer to the master protocol (nct04501978) * additional exclusion criteria: * pregnant women * nursing mothers * in addition, prior to the initial futility assessment which is performed when approximately 150 participants have been enrolled on brii-196/brii-198 and 150 on placebo, patients on high-flow oxygen or non-invasive ventilation (category 5 of the pulmonary ordinal outcome) will be excluded. these patients may be eligible for the trial if the initial futility assessment is passed by this agent.

Keywords: covid-19 covid 19 coronaviridae infections coronavirus infections rna virus infections virus infections nidovirales infections sars-cov-2 sars coronavirus activ-3 activ3 tico